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Biomedical subjects

C Dye

Publications and source records attributed to C Dye.

At least 55 records · Page 3Linked to original sources
PubMed1997

Multigenic drug resistance among inbred malaria parasites.

Recent population genetic studies on the malaria parasite Plasmodium falciparum have confirmed that selfing is more frequent where the transmission rate is lower, with inbreeding coefficients estimated to be 0.33 and 0.92 for sites in Tanzania and Papua New Guinea (PNG), respectively. These geographical differences in Plasmodium mating patterns have been linked to the rate of spread of chloroquine resistance CQR, which, according to some measures, has been slower in Tanzania than in PNG. It has been proposed that the former observation explains the latter, although the theoretical argument linking the two is based on limited simulation studies. Taking a more analytical approach here, we first establish the relevant relationship between the coefficient of inbreeding (F, within loci) and the recombination rate r, between loci, defining an 'effective recombination rate', r = r (1-F. We then show that the emergence of multigenic drug resistance can indeed be slowed (or even quickened) by more outcrossing, but only when resistance is determined by two or more genes, none of which independently confers significant protection. The resistance genes should both be initially rare, and subject to low selection pressure. The analysis does not completely discount the hypothesis that inbreeding significantly influences the spread of CQR, but we show that it can only do so under a restrictive set of conditions, and that these conditions are not satisfied by some laboratory and field data. We discuss some of the wider implications of these results for the evolution of multigenic resistance.

Animals↗
PubMed1997

Heterogeneities in the transmission of infectious agents: implications for the design of control programs.

From an analysis of the distributions of measures of transmission rates among hosts, we identify an empirical relationship suggesting that, typically, 20% of the host population contributes at least 80% of the net transmission potential, as measured by the basic reproduction number, R0. This is an example of a statistical pattern known as the 20/80 rule. The rule applies to a variety of disease systems, including vector-borne parasites and sexually transmitted pathogens. The rule implies that control programs targeted at the "core" 20% group are potentially highly effective and, conversely, that programs that fail to reach all of this group will be much less effective than expected in reducing levels of infection in the population as a whole.

Animals↗
PubMed1997

The epidemiology of canine leishmaniasis: transmission rates estimated from a cohort study in Amazonian Brazil.

We estimate the incidence rate, serological conversion rate and basic case reproduction number (R0) of Leishmania infantum from a cohort study of 126 domestic dogs exposed to natural infection rates over 2 years on Marajó Island, Pará State, Brazil. The analysis includes new methods for (1) determining the number of seropositives in cross-sectional serological data, (2) identifying seroconversions in longitudinal studies, based on both the number of antibody units and their rate of change through time, (3) estimating incidence and serological pre-patent periods and (4) calculating R0 for a potentially fatal, vector-borne disease under seasonal transmission. Longitudinal and cross-sectional serological (ELISA) analyses gave similar estimates of the proportion of dogs positive. However, longitudinal analysis allowed the calculation of pre-patent periods, and hence the more accurate estimation of incidence: an infection-conversion model fitted by maximum likelihood to serological data yielded seasonally varying per capita incidence rates with a mean of 8.66 x 10(-3)/day (mean time to infection 115 days, 95% C.L. 107-126 days), and a median pre-patent period of 94 (95% C.L. 82-111) days. These results were used in conjunction with theory and dog demographic data to estimate the basic reproduction number, R0, as 5.9 (95% C.L. 4.4-7.4). R0 is a determinant of the scale of the leishmaniasis control problem, and we comment on the options for control.

Animals↗
PubMed1997

Cutaneous leishmaniasis in the Peruvian Andes: factors associated with variability in clinical symptoms, response to treatment, and parasite isolation rate.

The severity of cutaneous leishmaniasis may be determined by host immunity, parasite virulence, and host or vector behavior. We performed a multivariate analysis to identify the main causes of the variability in clinical symptoms, response to treatment, and parasite isolation rate among Peruvian patients. The effect of host immunity was demonstrated first by the finding that secondary infections induced smaller lesions associated with a lower parasite isolation rate than did primary infections and, second, by the finding of fewer lesions in older patients. Phenotypic differences between parasite populations were suggested by the observation that the mean scar size and number varied between villages: patients had more scars in villages where the transmission rates were higher. Human behavior probably determined the site of lesions on the body, since most lesions in the cooler South were on the head, whereas in the North, lesions were equally frequent on the extremities. In addition, older patients, who were more likely infected through occupational exposure, had fewer head lesions. Geographic variation in the pattern of exposure to sandflies indicates that uta control strategies should be region specific.

Adolescent↗
PubMed1997

Differential application of lambda-cyhalothrin to control the sandfly Lutzomyia longipalpis.

To study the impact of residual pyrethroid insecticide on the abundance and distribution of peridomestic Lutzomyia longipalpis, the sandfly vector of visceral leishmaniasis in Brazil, lambda-cyhalothrin was applied at 20 mg a.i.m-2 in the following interventions: (i) spraying of all animal pens in a village (blanket coverage); (ii) treatment of a subset of animal pens, either by spraying, or by installation of insecticide-impregnated 1 m2 cotton sheets as 'targets' (focal coverage). By sampling with CDC light traps, and using a novel analytical approach, we detected a 90% reduction in Lu.longipalpis abundance in sprayed sheds of the focal intervention. However, there was no discernible effect on the abundance of other phlebotomines trapped in sheds, or on the abundance of Lu.longipalpis in untreated dining-huts and houses. This differential impact on Lu.longipalpis abundance is explained in terms of the disruption of male pheromone production. Treated targets were approximately half as effective as residual spraying in reducing the abundance of Lu.longipalpis in sheds. Following blanket intervention, the abundance of Lu.longipalpis in traps fell by only 45% (not significant): catches at untreated dining-huts actually increased, possibly because the blanket coverage diverted Lu.longipalpis away from major aggregation sites at animal pens. It is recommended that care be taken during vector control programmes to ensure that all potential aggregation sites are treated. The possible consequences of leaving some sites untreated include poor control of peridomestic sandfly abundance and an increase in the biting rate on dogs and humans.

Animals↗
PubMed1997

Cutaneous leishmaniasis in the Peruvian Andes: risk factors identified from a village cohort study.

Risk factors for cutaneous leishmaniasis were identified from a comparative study of transmission rates in 27 villages in the Departments of Lima, Ancash, and Piura in Peru. To evaluate regression analysis as a tool for the incrimination of sand fly vectors in the absence of other biologic evidence, univariate and multivariate logistic regression analyses were used to identify which of 14 variables (the abundance of nine sand fly species, four social factors, and region) predicted transmission rates in villages (incidence, active prevalence, or cumulative prevalence). In general, suspected or proven vectors (e.g., Lutzomyia peruensis) had the strongest associations with transmission rate, indicating that regression is a useful supplementary method of incriminating vectors. Regression was then used to quantify the importance of suspected risk factors. Transmission rate increased with the abundance of Lu. peruensis, Lu. ayacuchensis, Lu. noguchii, and, to a lesser extent, Lu. verrucarum and transmission was higher among villagers who slept more frequently in temporary shelters in crop areas. There were also weak effects of the number of dogs/ person (negative) and the number of persons/household (positive). Linear regressions failed to detect a threshold sand fly density below which transmission ceases. The minimal adequate multiple regression model explained 82% of the variance in village incidence rates. This model was used to predict the effect on incidence of reducing each of the four suspected vectors in northern and southern Peru. The results indicate that vector control programs in the south should aim at Lu. peruensis, Lu. verrucarum, and Lu. noguchii, but focus on Lu. ayacuchensis in the north.

Analysis of Variance↗
PubMed1996

Immunization coverage required to prevent outbreaks of dog rabies.

WHO recommends that 70% of dogs in a population should be immunized to eliminate or prevent outbreaks of rabies. This critical percentage (pc) has been established empirically from observations on the relationship between vaccination coverage and rabies incidence in dog populations around the world. Here, by contrast, we estimate pc by using epidemic theory, together with data available from four outbreaks in urban and rural areas of the USA, Mexico, Malaysia and Indonesia. From the rate of increase of cases at the beginning of these epidemics, we obtain estimates of the basic case reproduction number of infection, R0, in the range 1.62-2.33, implying that pc lies between 39% and 57%. The errors attached to these estimates of pc suggest that the recommended coverage of 70% would prevent a major outbreak of rabies on no fewer than 96.5% of occasions.

Animals↗
PubMed1996

The logic of visceral leishmaniasis control.

Mathematical models are used to compare the effectiveness of various untested, unused, and undeveloped methods for controlling canine and human zoonotic visceral leishmaniasis (ZVL), including insecticides, vaccines, killing serologically positive and sick dogs, and drugs. For given percentage changes in control parameters, insecticides are the most effective control method. Where transmission occurs peridomestically and vectors are accessible to treatment, as in parts of tropical America, insecticides are expected to reduce the incidence of human ZVL even more effectively than they reduce the prevalence of canine leishmaniasis, a result that should encourage properly designed vector control trials. The second best strategy is to reduce susceptibility to leishmaniasis by vaccinating people or dogs, or by eliminating childhood malnutrition where it is common. Both killing vectors and reducing susceptibility (by whatever means) are more effective than killing dogs or treating them with drugs. In Europe, where vector control is less likely to be successful and canine leishmaniasis is a major veterinary problem, a dog vaccine is highly desirable. Better drugs for dogs will help case management but, with regard to bringing down the incidence in the dog population, immunization is the ultimate goal.

Animals↗
PubMed1996

Falciparum malaria and climate change in the northwest frontier province of Pakistan.

Following a striking increase in the severity of autumnal outbreaks of Plasmodium falciparum during the last decade in the Northwest Frontier Province (NWFP) of Pakistan, the role of climatologic variables was investigated. A multivariate analysis showed that during the transmission season of P. falciparum, the amount of rainfall in September and October, the temperature in November and December, and the humidity in December were all correlated (r2 = 0.82) with two measures of P. falciparum, the falciparum rate (percent of slides examined positive for P. falciparum) since 1981 and the annual P. falciparum proportion (percent of all malaria infections diagnosed as P. falciparum) since 1978. Climatologic records since 1876 show an increase in mean November and December temperatures by 2 degrees C and 1.5 degrees C, respectively, and in October rainfall. Mean humidity in December has also been increasing since 1950. These climatologic changes in the area appear to have made conditions for transmission of P. falciparum more favorable, and may account for the increase in incidence observed in the NWFP in recent years.

Animals↗
PubMed1995

Extensive polymorphism at the Gp63 locus in field isolates of Leishmania peruviana.

Genetic diversity within and between tandemly arrayed copies of the Gp63 gene occurs in laboratory isolates of Leishmania spp., but the extent to which this represents natural genetic diversity has not been assessed. Here, the Gp63 locus is examined in 58 fresh isolates of L. peruviana, and clones derived from them, collected throughout the Peruvian Andes. Extensive polymorphism is observed, both in size of Gp63 containing chromosomes, and for restriction-fragment-length polymorphisms (RFLPs) at the Gp63 locus. All clones within an isolate are identical, including those with two distinct Gp63-hybridising chromosomal-sized pulsed-field gel electrophoresis (PFGE) bands, consistent with diploidy but with size differences in homologous chromosomes. For RFLP analysis, three enzymes were selected to cut within the coding region (PstI), in the intergenic region (SalI) and outside (EcoRI) the Gp63 gene cluster. PstI gave identical banding patterns across all isolates/clones. For EcoRI and SalI, all clones within an isolate were identical, but isolates were polymorphic for fragments at 13 (2-30 kb) and 8 (2.6-8.8 kb) different molecular mass locations generating 19 and 16 distinct RFLP patterns or genotypes for each enzyme, respectively. EcoRI restriction patterns, analysed by PFGE, were consistent with the presence of two clusters of Gp63 genes on each homologous chromosome, one contained within EcoRI fragments large enough to carry from 3 to 10 copies of the Gp63 gene, the second on fragments which could carry 1 or 2 copies of the gene. SalI patterns indicated variable restriction sites within clusters, but not within every intergenic region. A hierarchical analysis of variance of allele frequencies, expressed in terms of Wright's F-statistic, indicated significant barriers to gene flow at all levels, valleys within regions (north/south), villages within valleys, and individuals within villages. This extreme polymorphism at the Gp63 locus of L. peruviana demonstrates the great potential for generation of genetic diversity in parasite populations.

Animals↗
PubMed1995

Maintenance of a microparasite infecting several host species: rabies in the Serengeti.

Whether and how microparasites such as rabies persist in their host populations are among the fundamental questions of infectious disease epidemiology. Rabies is fatal disease of all mammalian species, but not all mammalian species can maintain the infection as reservoirs. The approach to control depends on which of the affected species do act as reservoirs. Bringing together old and new data, we examine here the role of wild and domestic animals in maintaining rabies in the Serengeti region of Tanzania, presenting our findings in two parts. In Part I, we argue that domestic dogs are the likely reservoirs because: (1) rabies has been continuously present in the dog population since its (re)introduction in 1977, whilst (2) wildlife cases have been very rare over this period, despite intensive study of Serengeti carnivores; (3) outbreaks of rabies in wild canids (jackals) elsewhere in Africa (Zimbabwe) have followed, rather than preceded, outbreaks in the dog population; (4) all viruses isolated from wild carnivores in the Serengeti ecosystem (including the Kenyan Masai Mara) are antigenically and genetically indistinguishable from the typical domestic dog strain; (5) dog rabies control in the Serengeti between 1958-77 apparently eliminated the disease from both dogs and wildlife. Having identified dogs as reservoirs, Part II explores some possible mechanisms of maintenance in dog populations. In theory, infection is more likely to be maintained at higher dog densities, and we provide evidence that rabies is maintained in one district with a dog density > 5/km2, but not in two other districts with densities < 1/km2. Because 5 dogs/km2 is much lower than the expected density required for persistence, we go on to investigate the role of atypical infections, showing: (1) from serology, that a substantial proportion of healthy dogs in the Serengeti have detectable serum levels of rabies-specific antibody; (2) from mathematical models that, whilst we cannot be sure what seropositivity means, persistence in low-density dog populations is more likely if seropositives are infectious carriers, rather than slow-incubators or immunes.

Animals↗
PubMed1995

Replication, differentiation, growth and the virulence of Trypanosoma brucei infections.

This study had 2 objectives: first, to investigate how the processes of slender form replication, of differentiation from dividing slender to non-dividing stumpy forms, and of stumpy mortality, combine to determine the initial (acute-phase) growth rate of Trypanosoma brucei populations; second, to determine how acute-phase growth rates influence parasite densities during the subsequent, chronic phase of infection. During the acute phase, slender and stumpy populations both grew approximately exponentially, the latter more slowly than the former. Mathematical models showed how this difference in slender and stumpy growth rates can be explained in terms of heterogeneous replication and differentiation rates. Stumpy life-expectancy was determined for one stock and found to be age-dependent with a half-life of 48-72 h, much larger than observed population doubling times of 5-10 h. A comparison of cloned stocks showed that the highest parasite densities during the chronic phase were associated with the highest acute-phase growth rates of both the whole parasite population and of the subpopulation of slender forms. By contrast, high chronic-phase parasitaemias artificially produced following rapid syringe passage were associated with low acute-phase growth rates of slender forms. Syringe-passaging is a laboratory procedure which selects for virulent parasites, but these parasites behave differently from naturally virulent stocks.

Animals↗
PubMed1995

Cutaneous leishmaniasis in the Peruvian Andes: an epidemiological study of infection and immunity.

A prospective longitudinal survey of cutaneous leishmaniasis (Leishmania peruviana) was carried out in Peru on a study population of 4716 persons living in 38 villages (Departments of Lima, Ancash and Piura). Demographic and clinical data were collected from all individuals, and a Montenegro skin test (MST) was carried out on 72% (3418) of the study population. Each household was revisited at 3-monthly intervals for up to 2 years to detect new leishmaniasis cases; 497 people received a second MST at the end of the study. Analysis of the epidemiological data indicated that (i) 17% (16/94) of all infections were subclinical, (ii) this percentage increased significantly with age, (iii) clinical infections led to 73.9% protective immunity (95% C.I. 53.0-85.5%) and relatively permanent MST responsiveness (recovery rate = 0.0098/year; 95% C.I. 0.000-0.020/year), (iv) sub-clinical infections led to protective immunity, which was positively correlated with their MST induration size (increasing by 17.9% per mm; P < 0.0001), and a mean MST recovery rate of 0.114/year (4/421 man-months), and (v) recurrent leishmaniasis was dominated by reactivations, not by reinfections.

Adolescent↗
PubMed1995

Measles vaccination policy.

Where immunization campaigns locally eliminate measles, it will be important to identify the vaccination policy most likely to prevent future epidemics. The optimum age for vaccination depends on the rate of decline of maternal antibody, because the presence of antibody reduces vaccine efficacy. The first part of this paper contains a quantitative reappraisal of the data on antibody decline and seroconversion rates by age. The decline in maternal antibody protection follows delayed exponentials, with delays of 2-4 months, and subsequent half-lives of 1-2 months. Using this result in an analytical mathematical model we find that the optimal age to administer a single dose of vaccine to children, which is independent of vaccine coverage, lies within the range 11-19 months. We also show that, where the optimal age cannot be met, it is better to err towards late rather than early vaccination. There are therefore two reasons why developing countries, which presently vaccinate during infancy because measles transmission rates are high should eventually switch to the second year of life. The possible gains from two-dose vaccination schedules are explored with respect to both coverage and efficacy. A two-dose schedule will be beneficial, in principle, only when there is a need to increase net vaccine efficacy, after coverage has been maximized with a one-dose schedule.

Antibodies, Viral↗
PubMed1994

Maximum likelihood for parasitologists.

In quantitative biology, observed data are fitted to a model that captures the essence of the system under investigation in order to obtain estimates of the parameters of the model, as well as their standard errors and interactions. The fitting is best done by the method of maximum likelihood, though least-squares fits are often used as an approximation because the calculations are perceived to be simpler. Here Brian Williams and Chris Dye argue that the method of maximum likelihood is generally preferable to least squares giving the best estimates of the parameters for data with any given error distribution, and the calculations are no more difficult than for least-squares fitting. They offer a relatively simple explanation of the methods and describe its implementation using examples from leishmaniasis epidemiology.

Journal Article↗